Biomedical subjects

Masahide Yamamoto

Publications and source records attributed to Masahide Yamamoto.

10 recordsLinked to original sources

PubMed2006

[Ischemic colitis following the treatment of acute hemorrhage in a patient with acquired hemophilia A].

A 66-year-old man with hypertension and hyperlipidemia developed a hemorrhagic stomal ulcer and massive hematoma of the face at 4 and 7 months, respectively, after fundusectomy for early gastric cancer. The diagnosis of acquired hemophilia A was made based on the marked prolongation of activated partial thromboplastin time, an extremely low factor VIII activity, and a very high-titer factor VIII inhibitor. After admission, oral prednisolone and cyclophosphamide were started. In addition, activated prothrombin complex concentrates and recombinant activated factor VII were intravenously administered which successfully controlled his hemorrhage. Only 1 week after the episode of bleeding, however, he complained of abdominal pain accompanied by watery stool with fresh blood. The diagnosis of ischemic colitis was made based on the clinical course and the findings on both CT-scan and colon fiberoscopy. The colitis spontaneously and quickly resolved with conservative observation. To the best of our knowledge, this is the first reported case of ischemic colitis that occurred in an acquired hemophilia patient without simultaneous administration of coagulation factors or antifibrinolytic agents. We should thus pay attention to the possible occurrence of thrombotic events even in acquired hemophilia patients in the presence of risk factors for thrombosis.

Acute Disease↗

PubMed2005

Intramolecular excimer emission of triply bridged [3.3.N](3,6,9)carbazolophanes.

The photophysical properties of a series of triply bridged [3.3.n](3,6,9)carbazolophanes ([3.3.n]Cz, n = 3, 4, 5, 6) were studied as a model compound for a fully overlapped carbazole excimer. In these [3.3.n]Cz molecules, a plane angle of the two carbazole moieties changed systematically from nearly parallel to oblique, with increases in the length of the methylene chain n bridging at the 9-position of each carbazole ring. Absorption bands of [3.3.n]Cz showed the blue-shift and the splitting for (1)L(a) <-- (1)A and (1)L(b) <-- (1)A transition bands of the reference carbazole monomer, respectively. These spectral changes in [3.3.n]Cz were explained by Kasha's molecular exciton theory with the distance r and dihedral angle theta between the carbazole moieties in the ground state. In both liquid and glass matrixes, [3.3.n]Cz showed intramolecular excimer emission. The emission peak wavelength changed from 409 nm (n = 6) to 480 nm (n = 3) depending on r in the ground state. The dependence of the peak wavelength on r clearly showed that relative configurations of carbazole moieties in the ground state were preserved even in the excimer states. The smaller radiative rate of the excimer emission than the reference monomer was explained by the dimer symmetry of [3.3.n]Cz.

Journal Article↗

PubMed2005

Calmodulin physically interacts with the erythropoietin receptor and enhances Jak2-mediated signaling.

Stimulation of the erythropoietin receptor (EpoR) induces a transient increase in intracellular Ca2+ level as well as activation of the Jak2 tyrosine kinase to stimulate various downstream signaling pathways. Here, we demonstrate that the universal Ca2+ receptor calmodulin (CaM) binds EpoR in a Ca2+-dependent manner in vitro. Binding studies using various EpoR mutants in hematopoietic cells showed that CaM binds the membrane-proximal 65-amino-acid cytoplasmic region (amino acids 258-312) of EpoR that is critical for activation of Jak2-mediated EpoR signaling. Structurally unrelated CaM antagonists, W-13 and CMZ, inhibited activation of Jak2-mediated EpoR signaling pathways, whereas W-12, a W-13 analog, did not show any significant inhibitory effect. Moreover, overexpression of CaM augmented Epo-induced tyrosine phosphorylation of the EpoR. W-13, but not W-12, also inhibited Epo-induced proliferation and survival. Together, these results indicate that CaM binds to the membrane-proximal EpoR cytoplasmic region and plays an essential role in activation of Jak2-mediated EpoR signaling.

Animals↗

PubMed2005

Photoinduced intramolecular charge separation in a polymer solid below the glass transition temperature.

Photoinduced intramolecular charge separation (CS) in a polar polymer glass, cyanoethylated pullulan (CN-PUL), was studied below the glass transition temperature (Tg=395 K). A series of three carbazole (Cz: donor)-cyclohexane (S: spacer)-acceptor (A: acceptor) molecules (Cz-S-A) was used as intramolecular donor-acceptor dyads. The photoinduced CS rate was evaluated by the fluorescence decay measurement at temperatures from 100 to 400 K. The CS rate (kCS) increased above 200 K even far below Tg where micro-Brownian motions of the whole polymer chain are frozen. Below 200 K, on the other hand, kCS showed weak dependence on temperature. The temperature dependence of kCS is discussed in terms of the dielectric relaxation time of the polymer matrix. Consequently, CS below Tg was well explained by a thermally nonequilibrium electron transfer (ET) formula above 200 K and by a two-mode quantum-mechanical ET formula below 200 K. The increase in kCS above 200 K is mainly caused by a thermally activated low-frequency matrix mode originating from the side-chain relaxation of polar cyano groups. The weak temperature dependence of kCS can be explained by a nuclear-tunneling effect caused by a high-frequency matrix mode (variant Planck's over 2piomegH=250 cm-1) and an intramolecular vibrational mode (variant Planck's over 2piomegaQ=1300 cm-1). The high-frequency mode of the polymer matrix was attributed to a vibrational or librational motion of polar groups in the CN-PUL glassy solid.

Journal Article↗

PubMed2005

Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.

The BCR/ABL tyrosine kinase inhibitor imatinib has shown remarkable efficacy in treating patients with chronic myelogenous leukemia (CML). In a small portion of patients treated with imatinib, however, the disease may progress to advanced stages, frequently accompanied by cytogenetic clonal evolution with the appearance of additional chromosomal aberrations besides the Philadelphia chromosome. Here we report the appearance of an inv(11)(p15q22) as a clonal evolution in a CML patient undergoing treatment with imatinib. Leukemic cells from the patient were found to express the fusion transcript of NUP98 and DDX10, which is in accordance with previously reported cases of de novo or therapy-related acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(p15q22). Although the patient showed resistance to imatinib with the disease rapidly progressing to blast crisis, sequence analysis failed to reveal any mutation in the kinase domain of BCR/ABL that would explain the imatinib resistance. Furthermore, ex vivo treatment of leukemic cells with imatinib significantly reduced tyrosine phosphorylation of CrkL, a target of the BCR/ABL kinase. These observations raise a possibility that the NUP98/DDX10 fusion might be involved in imatinib resistance as well as in acute transformation of CML.

Antineoplastic Agents↗

PubMed2004

The two major imatinib resistance mutations E255K and T315I enhance the activity of BCR/ABL fusion kinase.

The resistance to the tyrosine kinase inhibitor imatinib in BCR/ABL-positive leukemias is mostly associated with mutations in the kinase domain of BCR/ABL, which include the most prevalent mutations E255K and T315I. Intriguingly, these mutations have also been identified in some patients before imatinib treatment. Here we examined the effects of these mutations on the kinase activity of a BCR/ABL kinase domain construct that also contained the SH3 and SH2 domains. When expressed in COS7 cells, the BCR/ABL construct with either E255K or T315I exhibited not only the resistance to imatinib but also the increase in activity to induce autophosphorylation as well as tyrosine phosphorylation of various cellular proteins, which included STAT5. The mutant kinases also showed increased activities in in vitro kinase assays. These results raise a possibility that the major imatinib resistance mutations E255K and T315I may confer the growth advantage on leukemic cells to expand in the absence of selective pressure from imatinib treatment.

Animals↗

PubMed2004

Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers.

Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but the biological significance of DNA hypomethylation in carcinogenesis is less understood. The expression of Maspin (mammary serpin) in differentiated normal cells is regulated by epigenetic modifications in a cell-type-specific manner. Paradoxical Maspin expression due to epigenetic modification has been addressed in several cancer cell types. To elucidate the role of the Maspin gene in thyroid cancer, we studied methylation status in the promoter region and its expression in six human undifferentiated thyroid cancer cell lines and in specimens from 92 primary thyroid tumors, consisting of six follicular adenomas, 56 well-differentiated thyroid cancers (WDTCs), 17 poorly differentiated thyroid cancers (PDTCs) and 13 undifferentiated thyroid cancers (UDTCs). Three of the six cell lines overexpressed Maspin mRNA and its protein product, but the remaining three did not. The methylation status at the promoter region was inversely correlated with Maspin expression. In Maspin-negative cell lines, Maspin expression was induced by treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Immunoreactivity for Maspin protein was frequently detected in UDTCs (8/13, 62%) and PDTCs (7/17, 41%). Immunoreactivity for Maspin was diffusely positive in UDTCs, and was restricted to dedifferentiated components of the tumor in PDTCs. Positive immunoreactivity was infrequent in WDTCs (1/56, 2%), and all follicular adenomas and normal thyroid glands were completely negative. Their methylation status evaluated by the methylation-specific PCR method showed a good inverse correlation with their immunoreactivity in surgically resected specimens. Our data suggest that overexpression of Maspin by DNA hypomethylation is closely associated with morphological dedifferentiation in thyroid cancers.

Adenoma↗

PubMed2004

[An abdominal follicular dendritic cell tumor in Castleman's disease].

A 57-year-old man was referred to our hospital because of elevated ALP. CT and MRI scans together with abdominal angiography showed multiple masses in his abdomen and portal vein obstruction. A diagnostic laparoscopic examination revealed a tumor of 3 cm x 3 cm near the portal vein and para-aortic lymphadenopathy. Histopathological examination of the tumor showed abnormal follicles with poorly formed germinal centers, scattered large spindle cells with proliferation of small lymphocytes, and hypervascular interfollicular tissue. The spindle cells were positive for follicular dendritic cell markers CD21, CD35, and epithelial membrane antigen. The diagnosis was made of a follicular dendritic cell (FDC) tumor in Castleman's disease (CD) of the hyaline-vascular type. Although the portal vein was obstructed by the FDC tumor, blood flow to the liver was retained by collateral vein. The patient did not show any response to four courses of CHOP therapy and died of obstructive jaundice, biliary tract infection and sepsis. So far, 17 cases of FDC tumor complicating CD have been reported, with a poor prognosis in all cases.

Abdominal Neoplasms↗

PubMed2002

Endoscopic versus conventional open thyroid lobectomy for benign thyroid nodules: a prospective study.

The current study compared results between endoscopic thyroidectomy and conventional surgery in a prospective study. Twenty-two patients eligible for endoscopic thyroidectomy were evaluated. Patients were divided into group A, for conventional open thyroidectomy (n = 12), and group B, for endoscopic thyroidectomy (n = 10). Operative time, blood loss, postoperative complications and analgesic requirements, and time taken to return to normal activity were compared. Groups A and B were statistically balanced. Blood loss was significantly less in group B than in group A (11 versus 32 mL; P = 0.004), but no significant differences were observed in any of the other parameters. No postoperative complications (hemorrhage or recurrent laryngeal nerve paralysis) were present in either group. Compared with conventional surgery, endoscopic thyroidectomy for benign thyroid nodules was associated with less blood loss, although blood loss was minimal for both procedures. There were no practical differences in technical ability to perform.

Adult↗

PubMedDate not supplied

Synovial sarcoma of the thyroid. Report of a case with aspiration cytology findings and gene analysis.

BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also occur in the head and neck region, including the thyroid gland. Cytologic findings are important to differentiate the tumor from other types of neoplasms arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A palpable neck tumor was detected, and a computed tomography scan showed a thyroid tumor accompanied by destruction of the thyroid and cricoid cartilage. The results of a preoperative fine needle aspiration biopsy showed numerous spindle cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of which suggested a medullary carcinoma. The extirpated thyroid tissue weighed approximately 120 g, and a grayish white, elastic, solid tumor (6.8 x 6.5 cm) was present in the left lobe. Histologically, fasciculation of spindle cells that had proliferated solidly and densely was observed. Also, the expression of a chimera gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy is generally considered very difficult. The detailed cytologic findings observed here might be helpful with the differential diagnosis of thyroid neoplasms.

Biomarkers, Tumor↗